MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4⁺ T cells

The aberrant expression of interleukin-17 (IL-17) has been reported in the pathogenesis of autoimmune diseases, such as primary Sjögren's syndrome (pSS). However, the detailed mechanism remains poorly understood. We aim to characterize the expression of IL-17 in pSS and analyze the detailed underlying mechanism. IL-17 and microRNA miR-let-7d-3p expression were assayed by quantitative real-time PCR and Western blot, and proliferation-related protein expression was measured by Western blot. Luciferase reporter assays were performed to detect the direct regulation of IL-17 by miR-let-7d-3p. Expression of miR-let-7d-3p was negatively correlated with the expression of IL-17 in patients with pSS. Besides, the AKT1/mTOR signaling pathway was found critical for miR-let-7d-3p-mediated IL-17 expression. Furthermore, miR-let-7d-3p targeted AKT1 to bridge the regulation of IL-17. Finally, we verified AKT1 co-expression could rescue IL-17 downregulation caused by miR-let-7d-3p. Our study revealed novel mechanism that how did IL-17 was exactly modulated by miR-let-7d-3p and the potential of miR-let-7d-3p-AKT1-mTOR-IL-17 signaling as therapeutic targets for autoimmune diseases.